Byung Ryul Jeon

Is prostate-specific antigen effective for population screening of prostate cancer? A systematic review.

Background The effectiveness of prostate-specific antigen (PSA) for population screening has presented controversial results in large trials and prior reviews. We investigated the effectiveness of PSA population screening in a systematic review. Methods The study was conducted using existing systematic reviews. We searched Ovid MEDLINE, Embase, Cochrane library, and the major Korean databases. The quality of the systematic reviews was assessed by two reviewers independently using AMSTAR. Randomized controlled trials were assessed using the risk of bias tool in the Cochrane group. Meta-analyses were conducted using Review Manager. The level of evidence of each outcome was assessed using GRADE. Results Prostate-cancer-specific mortality was not reduced based on similar prior reviews (relative risk [RR] 0.93; 95% confidence interval [CI], 0.81-1.07, P=0.31). The detection rate of stage 1 prostate cancer was not greater, with a RR of 1.67 (95% CI, 0.95-2.94) and high heterogeneity. The detection rate of all cancer stages in the screening group was high, with a RR of 1.45 (95% CI, 1.13-1.85). No difference in all-cause mortality was observed between the screening and control groups (RR, 0.99; 95% CI, 0.98-1.01, P=0.50). Prostate-cancer-specific mortality, all-cause mortality, and diagnosis of prostate cancer at stages 3-4 showed moderate levels of evidence. Conclusions Differently from prior studies, our review included updated Norrköping data and assessed the sole effect of PSA testing for prostate cancer screening. PSA screening alone did not increase early stage prostate cancer detection and did not lower mortality.

Identification of a Novel Splicing Mutation in the ARSA Gene in a Patient with Late-infantile Form of Metachromatic Leukodystrophy

Metachromatic leukodystrophy (MLD; MIM 250100), a severe neurodegenerative disorder inherited as an autosomal recessive trait, is caused by mutations in the arylsulfatase A (ARSA) gene. Although several germ line ARSA mutations have been identified in patients with MLD of various ethnic backgrounds elsewhere in the world, no genetically confirmed cases of MLD have been reported in Korea. Recently, we identified a mutation in the ARSA gene of a Korean male with MLD. A male infant with late-infantile form of MLD had been admitted to our hospital for further examination. His neuromuscular symptoms, which included inability to walk at the age of 12 months, gradually worsened, even after allograft bone marrow transplantation; he died at the age of 9 yr. His elder brother had also been diagnosed with MLD. To confirm the presence of a genetic abnormality, all the coding exons of the ARSA gene and the flanking introns were amplified by PCR. A molecular analysis of the ARSA gene revealed both a novel heterozygous splicing mutation (c.1101+1G>T) in intron 6 and a heterozygous missense mutation in exon 2 (c.296G>A; Gly99Asp). The patients elder brother who had MLD is believed to have had the same mutation, which may be correlated with a rapidly deteriorating clinical course. This study identified a novel mutation in the ARSA gene, related to a late-infantile form of MLD with a lethal clinical course and suggested that molecular diagnosis of patients may be useful in early diagnosis and for deciding intervention measures for their family members.

Acute promyelocytic leukemia with trisomy 8 showing normal PML-RARA FISH signal patterns: diagnostic application of long-distance polymerase chain reaction in molecularly discrepant leukemia cases.

Dear Editor, In the recent published article “FISH-negative cryptic PMLRARA rearrangements detected by long-distance polymerase chain reaction and sequencing analyses: a case study and review of literature,” we have reviewed and listed most of the reported cases of cryptic PML-RARA rearrangements so far [1]. In this study, we report an additional rare case of PML-RARA fluorescence in situ hybridization (FISH)-negative acute promyelocytic leukemia (APL) associated with trisomy 8 and discuss briefly on the relatively high frequency of Korean APL patients showing cryptic PMLRARA rearrangements. This novel case was again analyzed and characterized at molecular level by applying longdistance polymerase chain reaction (LD-PCR). A 23-year-old male was referred to our hospital for further evaluation and treatment of ecchymosis and thrombocytopenia. Complete blood count results were: hemoglobin, 12.0 g/dL; platelet count, 36,000/μL; and white blood cell count, 3,940/μL. Leukemic blasts and promyelocytes accounted for 13% of total leukocytes. Bone marrow

Clinical Characteristics and ALB Gene Mutation Analysis of Korean Patients with Bisalbuminemia

BACKGROUND Bisalbuminemia is a hereditary or an acquired condition characterized by the presence of 2 albumin variants with different mobilities on serum protein electrophoresis (SPE). The clinical significance of bisalbuminemia has not been clearly established. However, some regions of the albumin variant may affect the biochemical analysis of biomolecules such as steroid or thyroid hormones by altering their albumin-binding affinities. In this study, we analyzed the clinical manifestations, genetic variations, and the albumin-binding characteristics in Korean patients with bisalbuminemia. METHODS We performed SPE for samples from 580 Korean subjects and identified bisalbuminemia on the basis of the results of SPE. The clinical and biochemical characteristics, ALB gene mutations, and the structures of the albumin variants of patients with bisalbuminemia were analyzed. RESULTS SPE showed bisalbuminemia in 2 patients. One patient showed a genetic variation known as Nagasaki-1 (Asp293Gly) and the other showed a hitherto unreported missense mutation (c.593A>T; Lys198Ile). In both cases, the serum concentrations of the substances with binding affinity for albumin were not affected, and the mutation sites of the albumin were not located with the protein-binding loci. CONCLUSIONS The 2 Korean patients with bisalbuminemia showed genetic variations, including a novel missense mutation. The ALB gene analysis with 3D modeling is useful for determining the nature of bisalbuminemia and for predicting the effects on the albumin-binding affinity of other biochemical compounds.

A Case of Chronic Myeloid Leukemia With Rare Variant ETV6/ABL1 Rearrangement

Dear Editor, The translocation (9;12)(q34;p13) ETV6/ABL1 rearrangement is a rare but recurrent chromosomal translocation associated with a variety of hematological malignancies, including CML, atypical CML, AML, and ALL [1]. The structure of the ETV6/ABL1 oncoprotein is similar to that of BCR/ABL1, and they initiate similar downstream pathways [2]. There are two ETV6/ABL1 fusion isoforms: the type A isoform, which fuses ETV6 exon 4 with ABL1 exon 2; and the type B isoform, which fuses ETV6 exon 5 with ABL1 exon 2 [3, 4]. To date, 30 cases of ETV6/ABL1 fusion have been reported [5, 6], and only one of these cases resulted in CML with positive BCR/ABL1 rearrangement [7]. Herein, we report a rare case of CML with ETV6/ABL1 rearrangement. A 54-yr-old male was admitted with persistent leukocytosis. Complete blood counts showed a white blood cell count of 21.7 ×10/L with 1% blasts, Hb of 126 g/L, and platelet count of 294 ×10/L. Physical examination was unremarkable. Bone marrow (BM) analysis showed typical characteristics of CML (Fig. 1A, B). Chromosomal analysis of the BM cells demonstrated a balanced t(9;12)(q34;p13) translocation, which was not the Philadelphia chromosome (Fig. 1C). FISH analysis with probes for BCR/ABL1 (Abbott Vysis, Des Plaines, IL, USA detected no fusion signal. However, reverse transcriptase (RT)-PCR analysis of the BCR/ ABL1 fusion transcripts yielded positive results; the reaction product was 700 bp long, indicating positive rearrangement and hence, presence of the P230 chimeric protein at the molecular level (Fig. 1D). To visualize the ETV6/ABL1 fusion signal, we prepared a mixture of two commercially available, locus-specific identifiers: a BCR/ABL1 dual color, dual fusion translocation probe, and an ETV6/RUNX1 extra signal dual color translocation probe (Abbott Vysis) (Fig. 1E, F). Metaphase and interphase FISH with the mixed BCR/ABL1 and ETV6/RUNX1 probes showed one yellow fusion signal at 9q34, which was derived from a green signal from ETV6 and a red signal from ABL1 (Fig. 1G, H). RT-PCR analysis of the ETV6/ABL1 fusion transcript was positive for the 1,141-bp product, indicating a type B fusion (Fig. 1D). After diagnosis, the patient was transferred to another hospital, and therefore, follow-up BM examination was not possible. ETV6/ABL1 rearrangement has been reported to result in enhanced tyrosine kinase activity and neoplastic transformation [3, 8]. A total of 13 cases of ETV6/ABL1-positive or atypical CML have been reported to date (Table 1) [5, 7]. Among those cases, including the present case, two were BCR/ABL1 fusion-positive and 11 were either unknown or negative for the BCR/ABL1 fusion. Both BCR/ABL1 fusion-positive cases presented with per-

Simultaneous translocation of both TCR Loci (14q11) with rare partner loci (Xq22 and 12p13) in a case of T-lymphoblastic leukemia.

The most common recurrent cytogenetic abnormalities in T-lymphoblastic leukemia (T-acute lymphoblastic leukemia [T-ALL]) involve T-cell receptor (TCR) loci and a variety of partner genes, including HOX11, HOX11L2, MYC, and TAL1. In this report, we present a rare case involving simultaneous translocation of the TCR α/δ loci with different partner loci (Xq22 and 12p13); this resulted in a poor prognosis. Chromosomal analysis showed 46,Y,t(X;14)(q22;q11.2),t(12;14)(p13;q11.2) and FISH analysis by using a T-cell receptor alpha delta DNA probe, Split Signal (DakoCytomation, Denmark), showed translocations at the same TCR α/δ locus on both chromosomes. FISH with 2 bacterial artificial chromosome clones showed break apart signal, which suggests involvement of the IRS4 gene. To our knowledge, this is the first report of T-ALL in which both TCR α/δ loci were translocated with different partner loci, and 1 of the partner loci, Xq22, was a rare translocation partner locus that included IRS4 gene.

Pulmonary infection caused by Mycobacterium neoaurum: the first case in Korea.

Mycobacterium neoaurum is rapidly growing mycobacteria that can cause human infections. It commonly causes bloodstream infections in immunocompromised hosts, and unlike other mycobacteria species, it rarely causes pulmonary infections. We confirmed the first pulmonary infection case in Korea caused by M. neoaurum using full-length 16S rRNA gene sequencing.

Clinical Usefulness of Human Epididymis Protein 4 in Lung Cancer

Human epididymis protein 4 (HE4) has been suggested as a useful new biomarker of lung cancer; however, few relevant large-scale studies have been published. In this study, we evaluated the utility of serum HE4 for lung cancer detection. HE4 levels were measured in serum samples from 100 lung cancer patients, 57 patients with benign lung diseases, and 274 healthy controls by using a chemiluminescent immunoassay, and variations in HE4 levels were analyzed by clinical status such as lung cancer, benign lung disease, and healthy condition, Tumor, Lymph Nodes, Metastasis (TNM) stage, tumor score, and histological cancer type. Lung cancer patients had significantly higher serum HE4 levels than patients with benign lung diseases and healthy controls (P<0.0001). The area under the ROC curve for HE4 was 0.84 (95% confidence interval, 0.78–0.89; P<0.0001) between lung cancer patients and healthy controls. Serum HE4 levels were significantly higher in patients with advanced disease (according to TNM stage) than in healthy controls (P<0.0001). HE4 levels were significantly elevated in patients with tumors of all types, those of different histological subgroups, and those with the smallest tumors (P=0.002). This report supports the potential of serum HE4 as an ancillary diagnostic marker for lung cancer detection.

First report of neutrophil involvement of exflagellated Plasmodium vivax microgametes.

Dear editorMalarial infections pass through multiple stages, beginning in the hepatic parenchymal cells where invading sporozoites ma-ture into schizonts. On maturation, these schizonts rupture and release merozoites into the bloodstream, which, in turn, target erythrocytes, leading to the clinical manifestations of the disease [1]. Exflagellation is characterized by thin, flagella-shaped mi-crogametes emerging from male malaria gametocytes; occurs in the midgut of the Anopheles mosquito; and has rarely been observed in peripheral blood specimens. Here, we present a case of Plasmodium vivax infection char-acterized by exflagellation of microgametes and accompanied by the unusual presence of exflagellated microgametes within the cytoplasm of peripheral leukocytes. To the best of our knowl-edge, this is the first report of neutrophil involvement of exflagel-lated Plasmodium. A pregnant 26-yr-old Pakistani woman presented with a fever >40°C lasting for 7 days. The patient, who arrived from Pakistan 10 days previously, had no medical history of malarial infection. She had been treated with non-steroidal anti-inflammatory drugs (NSAIDs), without improvement of symptoms, 4 days prior to her arrival at a local hospital. At presentation, the patient appeared acutely ill. Her blood pressure measured 90/50 mmHg, and body temperature was 37.2°C. Complete blood cell and differential counts revealed anemia with thrombocytopenia (white blood cell [WBC] 6.61× 10